DESCRIPTION: (Applicant's Description) Tobacco use remains the leading preventable cause of premature death in the U.S., and this public health problem will remain so if advances in the treatment of nicotine dependence do not occur. While the approved medications for smoking cessation to date are those that provide nicotine replacement, recent studies evaluating the effects of novel non-nicotine medications suggest that significant improvements in cessation rates may be possible. One of the most promising non-nicotine medications is bupropion (Zyban). Bupropion has been available as an antidepressant that increases dopamine availability and thus elevates mood, and will be FDA approved as a smoking cessation medication. Furthermore, it has been investigated as a medication for the treatment of attention deficit/hyperactivity disorder in youth. Because the efficacy of bupropion for adult smoking cessation is greater than nicotine replacement, and because the safety of bupropion has been shown in youth, it is the clear choice for investigation as a pharmacologic treatment for youth smoking cessation. Since the optimal dose for smoking cessation has not been assessed in youth, a dose ranging study to evaluate the safety and efficacy of bupropion for smoking cessation in youth is proposed. The proposed study is a randomized, double-blind, placebo-controlled clinical trial designed to assess (1) which bupropion dose, if any, increases abstinence rates over placebo, and (2) which factors, such as medication adherence, nicotine dependence, and motivation to quit, affect treatment outcome. There are a number of potential benefits from the proposed study. The results of the proposed study could lead to a better understanding of how to use a pharmacologic treatment for youth smoking cessation. Initiation of tobacco use is largely a sociocultural process, nicotine dependence is a medical condition whose treatment is optimized when the full armamentarium of medical care is provided. The proposed study will follow Agency for Health Care Policy and Research guidelines for smoking cessation, including a medical model approach that combines behavioral and pharmacologic intervention within a health care environment. While many studies have evaluated cessation methods for adults, there remains a dearth of research evaluating methods for enhancing youth smoking cessation. With so little research upon which to expand, the proposed study could lead to important new understandings regarding the process and mechanisms of youth smoking cessation.